期刊
ANTIOXIDANTS
卷 9, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/antiox9101005
关键词
synovial fibroblast; oxidative stress; nanomaterials
资金
- Baylor College of Medicine
- T32 awards from the National Institutes of Health [GM088129, AI053831, HL007676]
- F31 award from the National Institutes of Health [AR069960]
- National Institutes of Health [RR007495, HG006348, CA125123]
- Dan L. Duncan Comprehensive Cancer Center
- Cancer Prevention and Research Institute of Texas award [RP180672]
Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O-2(center dot-)) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the pathogenic functions of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and on the progression of an animal model of RA. We used human FLS from patients with RA to determine PEG-HCC internalization and effects on FLS cytotoxicity, invasiveness, proliferation, and production of proteases. We used the pristane-induced arthritis (PIA) rat model of RA to assess the benefits of PEG-HCCs on reducing disease severity. PEG-HCCs were internalized by RA-FLS, reduced their intracellular O-2(center dot-), and reduced multiple measures of their pathogenicity in vitro, including proliferation and invasion. In PIA, PEG-HCCs caused a 65% reduction in disease severity, as measured by a standardized scoring system of paw inflammation and caused a significant reduction in bone and tissue damage, and circulating rheumatoid factor. PEG-HCCs did not induce lymphopenia during PIA. Our study demonstrated a role for O-2(center dot-) and hydroxyl radicals in the pathogenesis of a rat model of RA and showed efficacy of PEG-HCCs in treating a rat model of RA.
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